Isoxicam is an active material of the 1,2-benzothiazine-1,1-dioxide group known from U.S. Pat. No. 3,787,324. It is used as a non-steroidal anti-inflammatory agent.
Since isoxicam is relatively poorly water-soluble, there arise difficulties with regard to the bioavailability with oral administration and, by suitable means, care must be taken that a sufficient resorption takes place which, above all, is independent of external conditions and of the patient and is uniform.
As a rule, in the case of poorly resorbed materials, the attempt is made either mechanically to comminute to a usable particle size the relatively large grained crystals obtained in the production or purification process of the active material or one so selects the crystallization conditions that, from the very beginning, crystals of the desired size are obtained.
In the case of mechanical comminution, for example micronization by means of jet mills, it is practically not possible to achieve a uniform particle size since the milling procedure produces fragments of the original crystals in the most varied sizes. Furthermore, jet mills are expensive not only in purchasing them but also in operation and achieve only a relatively small substance output per unit time.
The recrystallization of poorly soluble substances also leads, even when usable conditions with regard to solvents and crystallization conditions can be determined, to high substance losses because a complete recovery from the mother liquor is only possible with high costs. It is also difficult to achieve uniform crystal size.
In the case of precipitation processes which can give very finely divided particles, in most cases the precipitate is obtained amorphous or so finely crystalline that the further handling (centrifuging, filtration, drying, etc) is made extremely difficult.
Surprisingly, it has now been found that isoxicam is obtained crystalline in readily workable and outstandingly resorbable form.